Many clinical features of affective disorder, such as loss of appetite and libido, and diurnal variation in the intensity of symptoms, suggest impairment of hypothalamic-pituitary function. In addition, it is now well established that the hormones produced by the hypothalamic-pituitary axis are released by neurones which utilize the neurotransmitter amines hypothesized to be involved in affective disorder. For these reasons, the investigation of the various aspects of neuroendocrine function in patients with affective illness and in normal controls has assumed considerable importance. Several aspects of neuroendocrine function currently under investigation in our unit include studies of baseline levels, circadian patterns, variations during different phases of affective illness, and the effects of integrated challenge tests and clinical and experimental drugs (including amine precursors). Some findings during the last year include: TSH response to TRH was blunted in unipolar patients compared to both normals and bipolar depressed patients. A correlation between the TSH response and two CSF amine metabolites was found. In a regularly cycling post-menopausal bipolar patient, the baseline LH level was significantly lower during depression than in mania. In addition, studies concerning the hypothalamic-pituitary-adrenal axis suggest that this system and its amine regulators play an important role in affective illness.